Procedure for the deoxygenation of N-oxides of pyridine, quinoline and isoquinoline. (Machine-transl

专利摘要:
The present invention relates to a process for the catalytic deoxygenation of N-oxides of pyridine, quinoline and isoquinoline to the corresponding heterocyclic compounds derived from pyridine, quinoline and isoquinoline, by the use of pinacol (2,3-dimethyl-2,3 -butanediol) as a reducing agent in the presence of a molybdenum (VI) catalyst, in an organic solvent, at atmospheric pressure and at a temperature of 130ºC or, alternatively, by irradiation in a single-mode microwave oven at a maximum power of 150 w and at a temperature of 130º c, generating as main byproducts water and acetone. (Machine-translation by Google Translate, not legally binding)
公开号:ES2625739A1
申请号:ES201630064
申请日:2016-01-20
公开日:2017-07-20
发明作者:Roberto Sanz Díez；Rubén Rubio Presa；Manuel Ángel Fernández Rodríguez；Francisco Javier Arnáiz García；María Remedios Pedrosa Sáez
申请人:Universidad de Burgos；
IPC主号:

专利说明:

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PROCEDURE FOR THE DEOXIGENATION OF PIRIDINE N-OXIDES,
QUINOLIN AND ISOQUINOLINE
DESCRIPTION
OBJECT OF THE INVENTION
The present invention relates to a process for the catalytic deoxygenation of N-oxides of pyridine, quinoline and isoquinoline.
More specifically, the invention relates to a process for the catalytic deoxygenation of N-oxides of pyridine, quinoline or isoquinoline to compounds such as pyridine, quinoline or isoquinoline, respectively, by using pinacol (2,3-dimethyl-2,3 -butanediol) as a reducing agent in the presence of a molybdenum catalyst.
BACKGROUND OF THE INVENTION
Heterocyclic N-oxides have a high interest and importance as intermediates in the regioselective functionalization of the corresponding deoxygenated heterocycles, compounds with wide applicability in industries such as new materials, pharmaceutical, agrochemicals, etc. Therefore, the reaction of reduction of heterocyclic N-oxides to their corresponding nitrogen heterocycles constitutes a very useful process in organic synthesis.
The classic and more general methods for the deoxygenation of N-oxides of pyridine, quinoline and isoquinoline require the use of phosphorus compounds (III) such as PCl3 or metals such as Fe, Zn or Cu in stoichiometric amounts or even in excess. Some of these reduction processes can be found, for example, in (a) "The Chemistry of Heterocycles", Wiley-VCH, Weinheim, Germany, 2nd edn, 2003. (b) "Cu (I) -mediated deoxygenation of N- oxides to amines ”, Tetrahedron, 2007, 63, 126.
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More recently, catalytic methods have been developed using transition metal complexes such as Mo, Re, Pd or Cu, in the presence of various oxo-acceptors such as hydrogen, silanes, phosphines or diazo compounds. Some of these reduction processes can be found, for example, in (a) "Copper-catalyzed oxygen atom transfer of W-oxides leading to facile deoxygenation procedure applicable to both heterocyclic and amine W-oxides", Chem. Commun., 2015, 51, 7035. (b) "Efficient deoxygenation methodologies catalyzed by oxo-molybdenum and oxo-rhenium complexes", Coord. Chem. Rev., 2015, 284, 67-92.
JP 2012121844 A, "Method for producing pyridine compound by deoxygenating pyridine W-oxide compound", refers to a process for deoxygenation of W-oxidized pyridine in the presence of gold nanoparticles as a catalyst and a silylated derivative (phenyldimethylsilane or 1,1,3,3-tetramethyldisiloxane) as oxo-acceptor.
However, these previous methods have certain disadvantages, making it necessary to develop new methods of reducing heterocyclic W-oxides. Among the disadvantages of many of these methods known from the prior art for the deoxygenation of heterocyclic W-oxides are the use of reagents and reaction conditions that are incompatible with the presence of sensitive functional groups in the molecule such as olefins, carbonyls, nitriles or halogens. Likewise, many of these known methods give rise to by-products that are difficult to separate from the final product, which make tedious and expensive purification steps necessary to obtain the pure product. Many of the reducers used and by-products generated in the above methods are toxic, environmentally problematic and / or high cost.
On the other hand, patents ES 2381725 B2 "Procedure for the catalytic reduction of organic sulfoxides" and ES 2392998 B2 "Procedure for the catalytic reduction of nitroaromatic compounds" refer to the use of pinacol (2,3-dimethyl-2,3- butanediol) as a reducing agent for organic sulfoxides and nitroaromatic compounds in the presence of a molybdenum catalyst.
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Given the state of the art, the development of new catalytic methods that allow the use of cleaner, more manageable, general and efficient reducing agents continues to be studied. The new catalyst-reducing systems have as main challenges maintaining tolerance to potentially reducible groups and minimizing the formation of unwanted reaction byproducts.
The object of the present invention is, therefore, to provide a new process for the catalytic deoxygenation of heteroaromatic organic compounds having an N-oxide group, that is compounds of general formula (1), where R is an alkoxy, carboxyl, aryl group or heteroaryl, to nitrogenous heteroaromatic compounds (2), using pinacol as a reducer, which does not have the disadvantages of the aforementioned reduction procedures.
Ho oh
R1 — L-
[catT
V
(1) 0
image 1
Thus, the process for the deoxygenation of heterocyclic N-oxides of the present invention is based on the use of pinacol, as a reducing agent, an easily accessible and manageable compound; It generates easily separable and environmentally safe by-products and allows the obtaining of nitrogen heterocycles with high purity and high yield and without the need for expensive chromatographic separation procedures. The new process does not require inert atmospheres or high pressures, all reagents are solid or easily manipulated liquids. Additionally, the process of reduction of the present invention is highly selective, with no reduction of other functional groups occurring.
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In view of the foregoing, the present invention relates to a new process for reducing organic molecules. Specifically, it refers to a process for the catalytic deoxygenation of organic compounds of formula (1) that include an N-oxide functional group to heterodyl compounds of formula (2), by using pinacol (2,3-dimethyl-2 , 3-butanediol) as a reducing agent, using as a catalyst a molybdenum complex (VI),
Ho oh
image2
(1 OR 2)
where:
one
R represents a substituted or unsubstituted alkoxy, carboxyl, aryl or heteroaryl group;
[cat.] represents a catalyst of Mo (VI).
DETAILED EXHIBITION OF THE INVENTION
The present invention relates to a new process for reducing organic molecules. Specifically, it refers to a process for the catalytic deoxygenation of organic compounds of formula (1) that include an N-oxide functional group to heterodyl compounds of formula (2), by using pinacol (2,3-dimethyl-2 , 3-butanediol) as a reducing agent, using as a catalyst a molybdenum complex (VI),
HO OH
 R1 ^ [cat] / I l V'J ------------------------------- '  . R1t
 (1) 0  (2)
where:
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R in formula (1) and (2) represents a substituted or unsubstituted alkoxy, carboxyl, aryl or heteroaryl group;
[cat.] represents a catalyst of Mo (VI)
The process of the invention can be carried out in the absence of organic solvent, so that the process is simplified.
The process of the invention can be carried out in the presence of an organic solvent. In a preferred embodiment the organic solvent is dimethylacetamide (DMA). Preferably the process is carried out at atmospheric pressure and at a temperature of 130 ° C. In another preferred embodiment, the process is carried out by irradiation in a single-mode microwave oven at a maximum power of 150 W and at a temperature between 130 ° C and 140 ° C.
Preferably R is selected from substituted or unsubstituted alkoxy, carboxyl, aryl or heteroaryl groups such as benzyloxy, carboxyl, unsubstituted or substituted phenyl or pyridyl groups.
Preferably, the compounds of formula (1) are selected from the following compounds:
image3
Ph

'OR
image4
OR

"OR
image5
The process of the invention is carried out in the presence of a Mo (VI) catalyst. In a preferred materialization of the procedure of the
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Invention, the Mo (VI) catalyst is bis- (dimethylformamide) dichlorodioxomolibdene (VI), MoO2Cl2 (dmf) 2, where dmf = dimethylformamide. In another preferred materialization, the Mo (VI) catalyst is bis- (dimethylacetamide) dichlorodioxomolibdene (VI), MoO2Cl2 (dma) 2, where dma = dimethylacetamide
Preferably the amount of catalyst used is 5 mol%.
Preferably the amount of pinacol used in the process of the invention ranges between 1.1 and 3.0 equivalents.
The only by-products of the reaction obtained according to the process of the invention, from the oxidation of pinacol, are water and acetone, which allows to obtain the nitrogen heterocycle purely after a simple extraction.
The products obtained from the application of the process of the invention have a high purity and the yield of the process is high, this varying between approximately 77% and 91%.
The pinacol used as a reducing agent in the present process is an easily accessible and safe reagent from the point of view of its handling, which allows to carry out the process of the invention without the need for important protection systems or investments in terms of Safety is concerned, since the by-products obtained are acetone and water.
EXAMPLES
The process for the catalytic deoxygenation of organic compounds of formula (1) including an N-oxide functional group to heterocyclic compounds of formula (2), by utilizing pinacol (2,3-dimethyl-2,3-butanediol) as reducing agent, using bis- (dimethylacetamide) dichlorodioxomolibdene (VI) (MoO2Cl2 (dma) 2) catalyst of the invention is further illustrated by the following examples, which are not limiting the scope of the present invention.
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Example 1:
Deoxygenation of N-oxide from isoquinoline to isoquinoline at 130 ° C
image6
+
HO OH
image7
M0O2 Cl2 (dma) 2 (5 mo [%)
image8
, +
'OR
DMA ’130 ° C
A mixture of 76 mg of isoquinoline N-oxide (0.5 mmol), 59 mg of
Pinacol (0.55 mmol) and 9.4 mg of MoO2Cl2 (dma) 2 (5 mol%) in DMA (3 mL) was heated to 130 ° C in a 10 mL round bottom flask equipped with a cooling tube for 70 minutes. After that time, the mixture was allowed to cool to room temperature, 15 mL of AcOEt was added and the solution was washed with 0.5 M NaOH (3 x 3 mL). The organic phase was dried with anhydrous Na2SO4 and the solvents were removed under reduced pressure. 50 mg of isoquinoline were obtained (yield: 77%, purity> 95%) whose spectroscopic data are collected below: 1 H-NMR (300 MHz, CDCl 3): 5 (ppm): 9.23 (s, 1 H), 8.50 (d , J = 5.8 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 4.1 Hz, 1H), 7.71-7.51 (m, 3H). 13C-NMR (75.4 MHz, CDCh): 5 (ppm): 152.5 (CH), 142.9 (CH), 135.8 (C), 130.7 (CH), 128.7 (C), 127.6 (CH), 127.3 (CH ), 126.5 (CH), 120.5 (CH).
Example 2:
Deoxygenation of N-oxide from isoquinoline to isoquinoline under microwave radiation
pinacol (0.55 mmol) and 9.4 mg of MoO2Cl2 (dma) 2 (5 mol%) in DMA (1 mL) in a 10 mL microwave tube provided with septum was irradiated for 30 minutes at 130 ° C (temperature determined by a IR sensor located below the reaction cavity) and at a maximum power of 150 W in a single-mode microwave oven
image9
Dma
A mixture of 76 mg of isoquinoline N-oxide (0.5 mmol), 59 mg of
CEM Discover S-Class. After that time, the mixture was allowed to cool to room temperature, 15 mL of AcOEt was added and the solution was washed with 0.5 M NaOH (3 x 3 mL). The organic phase was dried with anhydrous Na2SO4 and the solvents were removed under reduced pressure. 52 mg of isoquinoline 5 were obtained (yield: 81%, purity> 95%). Alternatively, the reaction can be carried out without solvent increasing the amount of pinacol used to 177 mg.

权利要求:
Claims (11)
[1]
1.- Procedure for the catalytic deoxygenation of heteroaromatic organic compounds that have an N-oxide group, that is compounds of general formula (1) to nitrogenous heteroaromatic compounds of formula (2), characterized in that the reduction reaction is carried out by using pinacol, 2,3-dimethyl-2,3-butanediol, as a reducing agent, using a molybdenum catalyst (VI) as the reaction catalyst.
Ho oh
10
image 1
(1 OR 2)
where:
fifteen
one
R in formula (1) and (2) represents a substituted or unsubstituted alkoxy, carboxyl, aryl or heteroaryl group;
[cat.] represents a catalyst of Mo (VI).
[2]
2.- Procedure for catalytic deoxygenation N-heterocyclic oxides
one
according to claim 1, characterized in that R is selected from benzyloxy, carboxyl, unsubstituted or substituted phenyl groups and pyridyl groups.
[3]
3. Process for the catalytic deoxygenation of heterocyclic N-oxides according to claim 1, characterized in that the compounds of formula (1) are selected from:
image2
image3
OR
"OR
image4
[4]
4. - Procedure for the catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the catalyst of Mo (VI) is bis-
(dimethylformamide) dichlorodioxomolibdene (VI), MoO2Cl2 (dmf) 2, where dmf = dimethylformamide.
[5]
5. - Procedure for the catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the catalyst of Mo (VI) is bis-
(dimethylacetamide) dichlorodioxomolibdene (VI), MoO2Cl2 (dma) 2, where dma = dimethylacetamide.
[6]
6. - Procedure for the catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the reduction reaction is carried out
out at atmospheric pressure and at a temperature of 130 ° C.
[7]
7. - Procedure for catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the reduction reaction is carried out
2 0 conducted by irradiation in a single-mode microwave oven at a maximum power of 150 W and at a temperature of 130 ° C.
[8]
8. - Procedure for catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the reduction reaction is carried out
2 5 carried out in the absence or in the presence of an organic solvent.
[9]
9. - Procedure for catalytic deoxygenation N-heterocyclic oxides according to claim 8, characterized in that the organic solvent is
dimethylacetamide.
[10]
10. - Procedure for the catalytic deoxygenation N-heterocyclic oxides according to claim 1, characterized in that the amount of the catalyst is 5
5 mol%.
[11]
11. - Procedure for the catalytic deoxygenation of heterocyclic N-oxides according to claim 1, characterized in that the amount of pinacol used in the reduction reaction is 1.1 to 3.0 equivalents.

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ES2625739B2|2018-02-15|

引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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ES2392998A1|2011-05-30|2012-12-17|Universidad De Burgos|Procedure for the catalytic reduction of nitroaromatic compounds. |

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ES201630064A|ES2625739B2|2016-01-20|2016-01-20|Procedure for deoxygenation of N-oxides of pyridine, quinoline and isoquinoline.|ES201630064A| ES2625739B2|2016-01-20|2016-01-20|Procedure for deoxygenation of N-oxides of pyridine, quinoline and isoquinoline.|